CXCR4 has gained tremendous attention over the last decade, since it was found to be up-regulated in a wide variety of cancer types, in addition to its role in human immunodeficiency virus infection. Molecular imaging of CXCR4 with small molecules, peptides, and antibodies has been a vibrant research area over the last several years. In this review article, we will summarize the current status of imaging CXCR4 with fluorescence, bioluminescence, positron emission tomography, and single-photon emission computed tomography techniques. Since each molecular imaging modality has its own strengths and weaknesses, dualmodality probes that can be detected by more than one imaging techniques have also been investigated. Noninvasive visualization of CXCR4 expression has potential clinical applications in multiple facets of patient management. While big strides have been made over the last several years in the development of CXCR4- targeted imaging probes, clinical translation and investigation of these agents in cancer patients are eagerly awaited. Since CXCR4 is also involved in many other diseases beyond cancer, these clinically translatable probes can also play multiple roles in other pathological disorders such as myocardial infarction and several immunodeficiency disorders.